Liver-specific overexpression of scavenger receptor BI decreases levels ofvery low density lipoprotein ApoB, low density lipoprotein ApoB, and high density lipoprotein in transgenic mice

Scavenger receptor BI (SR-BI) is known to mediate the selective uptake of h igh density lipoprotein (HDL) cholesteryl ester (CE) in liver and steroidog enic tissues. To evaluate the role of SR-BI in plasma lipoprotein metabolis m, we have generated transgenic mice with liver-specific overexpression of murine SR-BI, On a chow diet SR-BI transgenic (SR-BI Tg) mice have decrease d HDL-CE, apoA-I, and apoA-II levels; plasma triglycerides, low density lip oprotein (LDL) cholesterol, and very low density lipoprotein (VLDL) and LDL apoB were also decreased, compared with control mice. Turnover studies usi ng non-degradable CE and protein labels showed markedly increased total and selective uptake of HDL-CE in the liver and increased HDL protein cataboli sm in both liver and kidney. To evaluate the changes in apoB further, mice were challenged with high fat, high cholesterol diets. In SR-BI Tg mice pla sma apoB levels were only 3-15% of control levels, and the dietary increase in VLDL and LDL apoB was virtually abolished. These studies show that stea dy state overexpression of hepatic SR-BI reduces HDL levels and increases r everse cholesterol transport. They also indicate that SR-BI can play a role in the metabolism of apoB-containing lipoproteins. The dual effects of inc reased reverse cholesterol transport and lowering of apoB-containing lipopr oteins that result hom hepatic SR-BI overexpression could have anti-atherog enic consequences.